We propose to investigate the influence of aging on the intestinal absorption of vitamins A, D, and E and the long-chain fatty acids, oleic and linoleic. Absorption will be studied at 6-month intervals throughout the lifespan of male Sprague-Dawley rats raised in our research vivarium. Initially, we will study uptake of lipid nutrients in vitro by everted gut sacs immersed in micellar solutions containing individual lipid-soluble nutrients and a nonabsorbable marker. Our next series of studies will utilize a single-pass technique in vivo to assess the influence of aging on lipid nutrient absorption when maximal surface area is exposed to the perfusate. Next, we plan to investigate the influence of aging both on the exit of lipid nutrients from th enterocytes and on their transport into the lymphatic and portal circulations. Rats with bile and lymph fistulas will be perfused with lipid nutrients, and the appearance rates of the nutrients in lymph and bile will be assessed. Several mechanisms which may cause age-related changes in absorption will be investigated. The first will be the thickness of the unstirred water-layer at th luminal cell membrane. Its thickness will be studied in vitro by measuring the half-time required for a change in the streaming potential to develop across the intestinal wall. The unstirred water-layer thickness in vivo will also be studied by measuring changes in the absorption rate of specific probe molecules at varying rates of intestinal perfusion. A second major mechanism which may be responsible for age-related alterations in the absorption of lipid nutrients is change in the permeability of the absorptive cell membranes. It will be studied by using different-sized homologues of polyethylene glycol which will be used as probe molecules to study permeability changes in perfused intestinal segments. A permeability profile will be obtained for each age group. Age-related changes in the paracellular route of absorption and in the intra-cellular cytosol binding proteins will also be investigated.